How methionyl-tRNA synthetase creates its amino acid recognition pocket upon L-methionine binding

J Mol Biol. 2001 Mar 2;306(4):863-76. doi: 10.1006/jmbi.2001.4408.


Amino acid selection by aminoacyl-tRNA synthetases requires efficient mechanisms to avoid incorrect charging of the cognate tRNAs. A proofreading mechanism prevents Escherichia coli methionyl-tRNA synthetase (EcMet-RS) from activating in vivo L-homocysteine, a natural competitor of L-methionine recognised by the enzyme. The crystal structure of the complex between EcMet-RS and L-methionine solved at 1.8 A resolution exhibits some conspicuous differences with the recently published free enzyme structure. Thus, the methionine delta-sulphur atom replaces a water molecule H-bonded to Leu13N and Tyr260O(eta) in the free enzyme. Rearrangements of aromatic residues enable the protein to form a hydrophobic pocket around the ligand side-chain. The subsequent formation of an extended water molecule network contributes to relative displacements, up to 3 A, of several domains of the protein. The structure of this complex supports a plausible mechanism for the selection of L-methionine versus L-homocysteine and suggests the possibility of information transfer between the different functional domains of the enzyme.

MeSH terms

  • Allosteric Regulation
  • Allosteric Site
  • Amino Acid Sequence
  • Binding, Competitive
  • Crystallization
  • Crystallography, X-Ray
  • Escherichia coli / enzymology*
  • Homocysteine / metabolism
  • Hydrogen Bonding
  • Methionine / chemistry
  • Methionine / metabolism*
  • Methionine-tRNA Ligase / chemistry*
  • Methionine-tRNA Ligase / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Substrate Specificity
  • Water / chemistry
  • Water / metabolism


  • Water
  • Homocysteine
  • Methionine
  • Methionine-tRNA Ligase

Associated data

  • PDB/1F4L